A massive new analysis involving more than 200 authors has uncovered a genetic locus that is more strongly associated with suicide attempt than psychiatric disorders or related traits.
The discovery helps disentangle the genetic etiology of suicidality, which could lead to more targeted prevention strategies.
The study emerged from the International Suicide Genetics Consortium and was led in part by co-first author JooEun Kang, an M.D./Ph.D. student, and senior author Douglas Ruderfer, Ph.D., an associate professor of biomedical informatics and psychiatry and behavioral sciences, both of Vanderbilt University Medical Center. Results were published in the journal Biological Psychiatry.
Eighteen Cohorts Unite
The genome-wide association study (GWAS) compared 29,782 cases of suicide attempt to 519,961 non-suicidal cases. Approximately 20 percent of suicide-attempt cases ended fatally.
Amassing the dataset were researchers from 18 cohorts worldwide, including the Psychiatric Genomics Consortium and the German Borderline Genomics Consortium, among others.
“Our study is notable for providing evidence of genetic influences on suicide attempt that are not mediated by psychiatric disorders.”
Each cohort contributed data from at least 200 cases that underwent standard genotyping and quality control leaving more than 7.7 million single nucleotide polymorphisms for analysis across cohorts.
The enormous dataset is nearly five times larger than any previous GWAS of suicide attempt, Kang said.
Teasing Out Other Factors
Suicide attempt occurs in approximately 0.5 to 5 percent of the global population and is historically tied to psychiatric illness, trauma and risk-seeking behavior. The authors cite several GWAS analyses that not only suggest suicide attempt is heritable, but that it also shares genetic underpinnings with a particular psychiatric illness – major depressive disorder (MDD).
“This genetic overlap, along with the high prevalence of MDD in the population, make it a particularly salient risk factor,” they wrote.
The research team confirmed these associations in the first step of their analysis. Then, to tease apart psychiatric illness and suicide attempt, the researchers removed the genetic contribution of MDD from suicide attempt. By doing so, they identified variations in a genomic region that contributed to suicide attempt more strongly than psychiatric disorders.
The researchers also identified significant genetic overlap between suicide attempt and non-psychiatric traits, such as smoking, sleep disturbances, lower socioeconomic status or education, and poorer overall health.
Together, the results indicate that a substantial portion of the heritability of suicide attempt is completely independent of psychiatric disorders.
Connections to Care
“Beyond its sheer scale, our study is notable for providing evidence of genetic influences on suicide attempt that are not mediated by psychiatric disorders, while also implicating shared biology between suicide attempt and specific non-psychiatric risk factors,” Ruderfer said.
The work complements other research by Ruderfer and colleagues that harnesses large datasets to dive into suicide-risk etiology. Artificial intelligence and EHRs have opened doors to help translate such findings into clinical settings.
Ruderfer acknowledges more work is required before the groundbreaking information about genetic loci may directly benefit clinic patients. Despite including African American and East Asian cohorts, for example, 90 percent of cases were of European ancestry which could limit broad applicability.
Still, the statistical power afforded by the study makes its results tough to ignore.
“Many genetic variants exert influence on suicide attempt independent of their influence on psychiatric disorders,” Ruderfer emphasized. “Additional work is necessary to tease the biological relationships apart to better understand possible causal pathways between genetics, risk factors and suicide attempt.”